Trifluridine (also known as α,α,α-trifluorothymidine. Hereinafter, also referred to as “FTD”) manifests antitumor effects by DNA synthesis inhibition from an action of inhibiting thymidylate production and by DNA function blocking from incorporation into DNA. Meanwhile, tipiracil hydrochloride (chemical name: 5-chloro-6-[(2-iminopyrrolidine-1-yl)methyl]pyrimidine-2,4(1H,3H)-dione hydrochloride. Hereinafter, also referred to as “TPI”) has an action of inhibiting thymidine phosphorylase. It is known that antitumor effect of FTD is enhanced by TPI that suppresses in vivo decomposition of FTD by thymidine phosphorylase (Patent Literature 1). Currently, an antitumor agent containing FTD and TPI at a molar ratio of 1:0.5 (hereinafter, also referred to as an “FTD/TPI combination drug”) is under development as a therapeutic agent for a solid cancer such as colorectal cancer (Non-Patent Literatures 1 and 2).
Furthermore, combination therapies to enhance the antitumor effect of an FTD/TPI combination drug have been studied, and the combined effect of the combination drug and irinotecan and oxaliplatin have been suggested so far (Non-Patent Literatures 3 and 4).
Meanwhile, in recent years, development of a drug targeting a molecule involved in angiogenesis or cell proliferation such as Vascular Endothelial Growth Factor (hereinafter, VEGF) and Epidermal Growth Factor Receptor (hereinafter, EGFR) is actively performed. For example, as a molecular target drug for VEGF, bevacizumab, which is an anti-VEGF humanized monoclonal antibody, is clinically used as a therapeutic agent for a carcinoma such as colorectal cancer, non-small cell lung cancer, breast cancer and renal cell cancer. In addition, as a molecular target drug for EGFR, cetuximab, which is an anti-EGFR human/mouse chimeric monoclonal antibody, is clinically used as a therapeutic agent for colorectal cancer and head and neck cancer, and panitumumab, which is an anti-EGFR human-type fully monoclonal antibody, is clinically used as a therapeutic agent for colorectal cancer, respectively (Non-Patent Literatures 5, 6 and 7).
As described above, although developments of a therapy including an FTD/TPI combination drug are energetically performed, a combination therapy using an FTD/TPI combination drug and a molecular target drug for VEGF or EGFR, is not known at all.